Abstract

Background Severe anaemia is a leading cause of paediatric admission to hospital in Africa; post-discharge outcomesremain poor, with high 6-month mortality (8%) and re-admission (17%). We aimed to investigate post-dischargeinterventions that might improve outcomes.Methods Within the two-stratum, open-label, multicentre, factorial randomised TRACT trial, children aged 2 monthsto 12 years with severe anaemia, defined as haemoglobin of less than 6 g/dL, at admission to hospital (three inUganda, one in Malawi) were randomly assigned, using sequentially numbered envelopes linked to a second nonsequentiallynumbered set of allocations stratified by centre and severity, to enhanced nutritional supplementationwith iron and folate-containing multivitamin multimineral supplements versus iron and folate alone at treatmentdoses (usual care), and to co-trimoxazole versus no co-trimoxazole. All interventions were administered orally andwere given for 3 months after discharge from hospital. Separately reported randomisations investigated transfusionmanagement. The primary outcome was 180-day mortality. All analyses were done in the intention-to-treat population;follow-up was 180 days. This trial is registered with the International Standard Randomised Controlled Trial registry,ISRCTN84086586, and follow-up is complete.Findings From Sept 17, 2014, to May 15, 2017, 3983 eligible children were randomly assigned to treatment, and followedup for 180 days. 164 (4%) were lost to follow-up. 1901 (95%) of 1997 assigned multivitamin multimineral supplement,1911 (96%) of 1986 assigned iron and folate, and 1922 (96%) of 1994 assigned co-trimoxazole started treatment. By day180, 166 (8%) children in the multivitamin multimineral supplement group versus 169 (9%) children in the iron andfolate group had died (hazard ratio [HR] 0·97, 95% CI 0·79–1·21; p=0·81) and 172 (9%) who received co-trimoxazoleversus 163 (8%) who did not receive co-trimoxazole had died (HR 1·07, 95% CI 0·86–1·32; p=0·56). We found noevidence of interactions between these randomisations or with transfusion randomisations (p>0·2). By day 180,489 (24%) children in the multivitamin multimineral supplement group versus 509 (26%) children in the iron and folategroup (HR 0·95, 95% CI 0·84–1·07; p=0·40), and 500 (25%) children in the co-trimoxazole group versus 498 (25%) childrenin the no co-trimoxazole group (1·01, 0·89–1·15; p=0·85) had had one or more serious adverse events. Most seriousadverse events were re-admissions, occurring in 692 (17%) children (175 [4%] with at least two re-admissions).Interpretation Neither enhanced supplementation with multivitamin multimineral supplement versus iron andfolate treatment or co-trimoxazole prophylaxis improved 6-month survival. High rates of hospital re-admissionsuggest that novel interventions are urgently required for severe anaemia, given the burden it places on overstretchedhealth services in Africa.